PROSTAGLANDIN SYNTHESIS INHIBITION STIMULATES LITHIUM REABSORPTION IN HENLE LOOP IN RATS

The effect of prostaglandin (PG) synthesis inhibition on tubular lithium (Li) handling in the rat was studied by micropuncture at the late proximal (LPT) and early distal (EDT) tubules. Animals received no treatment (N = 7), meclofenamate (MECLO; 5 mg/kg i.p. and 5 mg/kg i.v.; N = 7) or indomethacin (INDO, 1 mg/kg i.v.; N = 6). Whole kidney fractional Li excretion fell from 26.2 +/- 1.5% in control rats to 12.8 +/- 1.3% and 14.6 +/- 1.3% in MECLO and INDO treated rats. Fractional delivery of Li to the LPT was not affected by PG synthesis inhibition. All of the rise in tubular Li reabsorption took place between the LPT and EDT; at the EDT fractional Li delivery fell from 32.3 +/- 2.0% in the control group to 19.1 +/- 1.6% and 20.0 +/- 1.4% in the rats given MECLO or INDO. Water reabsorption between the LPT and EDT also increased. The tubular fluid/plasma Li concentration ratio ([T/P]Li) at the LPT was approximately 1.15 in all groups of rats. At the EDT, this ratio was approximately 1.06 in control rats, but only approximately 0.82 (P < 0.01) in rats subjected to PG synthesis inhibition. The finding that the [T/P]Li fell from values exceeding unity at the LPT to values below unity at the EDT during PG synthesis inhibition indicates that reabsorption of Li between these sites was stimulated to a greater extent than that of water. This dissociation strongly suggests that at least part of the increased Li reabsorption between the LPT and EDT took place in the water-impermeable thick ascending limb. We conclude: (1) Li reabsorption lags behind that of water in the proximal convoluted tubules; (2) Li reabsorption between the LPT and EDT is stimulated during PG synthesis inhibition, at least in part in the thick ascending limb of Henle's loop; (3) the fall in Li clearance during PG synthesis inhibition does not reflect stimulated reabsorption in the proximal convoluted tubules in the rat.